title: Semaphorin3E-induced inflammation contributes to insulin resistance in dietary obesity.
abstract: Semaphorins and their receptors (plexins) are axon-guiding molecules that regulate the development of the nervous system during embryogenesis. Here we describe a previously unknown role of class 3 semaphorin E (Sema3E) in adipose tissue inflammation and insulin resistance. Expression of Sema3E and its receptor plexinD1 was upregulated in the adipose tissue of a mouse model of dietary obesity. Inhibition of the Sema3E-plexinD1 axis markedly reduced adipose tissue inflammation and improved insulin resistance in this model. Conversely, overexpression of Sema3E in adipose tissue provoked inflammation and insulin resistance. Sema3E promoted infiltration of macrophages, and this effect was inhibited by disrupting plexinD1 expression in macrophages. Disruption of adipose tissue p53 expression led to downregulation of Sema3E expression and improved adipose tissue inflammation. These results indicate that Sema3E acts as a chemoattractant for macrophages, with p53-induced upregulation of Sema3E expression provoking adipose tissue inflammation and systemic insulin resistance in association with dietary obesity.
authors.affiliation: Department of Cardiovascular Science and Medicine, 1-8-1 Inohana, Chuo-ku, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Shimizu
authors.forename: Yohko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Junji
authors.initials: J
authors.lastname: Moriya
authors.forename: Aika
authors.initials: A
authors.lastname: Nojima
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Uemura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Tohru
authors.initials: T
authors.lastname: Minamino
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D059305:Diet, High-Fat; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D039942:Neuropilin-1 / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C473552:Plxnd1 protein, mouse; D034741:RNA, Small Interfering; D039961:Semaphorins; D016159:Tumor Suppressor Protein p53; D039942:Neuropilin-1; D040301:Vascular Endothelial Growth Factor Receptor-2